Size‐Dependent EPR Effect of Polymeric Nanoparticles on Tumor Targeting

Abstract

Passive targeting of large nanoparticles by the enhanced permeability and retention (EPR) effect is a crucial concept for solid tumor targeting in cancer nanomedicine. There is, however, a trade-off between the long-term blood circulation of nanoparticles and their nonspecific background tissue uptake. To define this size-dependent EPR effect, we designed near-infrared fluorophoreconjugated polyethylene glycols (PEG-ZW800s; 1-60 kDa) and evaluated their biodistribution, pharmacokinetics, and renal clearance in tumor-bearing mice. The targeting efficiency of sizevariant PEG-ZW800s was investigated in terms of tumor-to-background ratio (TBR). Interestingly, smaller sized PEGs (≤20 kDa, 12 nm) exhibited significant tumor targeting with minimum to no nonspecific uptakes, while larger sized PEGs (>20 kDa, 13 nm) accumulated highly in major organs, including the lungs, liver, and pancreas. Among those tested, 20 kDa PEG-ZW800 exhibited the highest TBR, while excreting unbound molecules to the urinary bladder. This result lays a foundation for engineering tumor-targeted nanoparticles and therapeutics based on the sizedependent EPR effect.

Redox‐Responsive Self‐Assembled Nanoparticles for Cancer Therapy

“…It promotes the selective distribution of nanoparticles with a diameter of 100-400 nm (optimal size selection) in tumor tissues, so it can increase drug efficacy and reduce systemic side effects. [7,8] To further enhance accumulation, as well as maintain the plasma concentration of antitumor drugs in tumor sites and decrease their side effects on normal tissues, it is increasingly popular to design a vector that controls drug release spatially and temporally. As a result, smart nanocarriers with stimuli-sensitive characters that are influenced by various external and internal stimuli have been studied in great detail.…”

Epigallocatechin-3-Gallate-Loaded Gold Nanoparticles: Preparation and Evaluation of Anticancer Efficacy in Ehrlich Tumor-Bearing Mice

“…Nanoparticle size and polydispersity index are known to affect their colloidal stability and in vivo biodistribution and ability to deliver their cargo to specific sites in the body [42,43]. For the successful delivery of anticancer drugs, it was shown that a smaller nanoparticle size facilitates passive accumulation in solid tumors through the enhanced permeability and retention effect [43,44]. The effect of EGCG/HAuCl 4 molar ratio on nanoparticle size and polydispersity index is shown in Table 1.…”

“…The enhanced anticancer efficacy observed for EGCG-GNPs compared with EGCG alone might be attributed to several reasons. First, the small size and negative charge of the nanoparticles could help increase their circulation time in the blood and thus enhance their accumulation in tumors through the enhanced permeability and retention effect [43,44]. Second, the observed sustained drug release could help the nanoparticles maintain their cargo until reaching the tumor site, which in turn increases drug accumulation in the tumor.…”

Design of Targeted Nanostructured Coordination Polymers (NCPs) for Cancer Therapy

“…A thorough knowledge of the physical properties (e.g., size, surface charge, shape, and mechanical strength) and chemical attributes of nanoparticles facilitates their application in biomedicine [55]. Specifically, nanoparticles in the range 10-100 nm can passively target tumors by freely passing through large pores (40 nm to 1 um in size) and achieve higher intra-tumoral accumulation [56] due to the highly permeable blood vessels provoked by the rapid and defected angiogenesis and dysfunctional lymphatic drainage [57]. In this sense, although the wide variety of NCPs-based nano-systems are expected to accumulate in tumors through the EPR effect, one of the most challenging goals has been addressing these nano-constructs toward individualized therapy and cancer treatment, especially based on the identification of cancer biomarkers [58].…”